molecules
Article
Simultaneous Predictions of Chemical and Phase Equilibria in
Systems with an Esterification Reaction Using PC-SAFT
Moreno Ascani, Gabriele Sadowski
Citation: Ascani, M.; Sadowski, G.;
Held, C. Simultaneous Predictions of
Chemical and Phase Equilibria in
Systems with an Esterification
Reaction Using PC-SAFT. Molecules
2023, 28, 1768. https://doi.org/
10.3390/molecules28041768
Academic Editor: Erich A. Müller
Received: 30 December 2022
Revised: 10 February 2023
Accepted: 11 February 2023
Published: 13 February 2023
Copyright: © 2023 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
Molecules 2023, 28, 1768. https://doi.org/10.3390/molecules28041768
and Christoph Held *
Laboratory of Thermodynamics, Department of Biochemical and Chemical Engineering,
TU Dortmund University, Emil-Figge Str. 70, 44277 Dortmund, Germany
* Correspondence: christoph.held@tu-dortmund.de; Tel.: +49-2317552086
Abstract: The study of chemical reactions in multiple liquid phase systems is becoming more and
more relevant in industry and academia. The ability to predict combined chemical and phase equilib-
ria is interesting from a scientific point of view but is also crucial to design innovative separation
processes. In this work, an algorithm to perform the combined chemical and liquid–liquid phase
equilibrium calculation was implemented in the PC-SAFT framework in order to predict the thermo-
dynamic equilibrium behavior of two multicomponent esterification systems. Esterification reactions
involve hydrophobic reacting agents and water, which might cause liquid–liquid phase separation
along the reaction coordinate, especially if long-chain alcoholic reactants are used. As test systems,
the two quaternary esterification systems starting from the reactants acetic acid + 1-pentanol and
from the reactants acetic acid + 1-hexanol were chosen. It is known that both quaternary systems
exhibit composition regions of overlapped chemical and liquid–liquid equilibrium. To the best of
our knowledge, this is the first time that PC-SAFT was used to calculate simultaneous chemical and
liquid–liquid equilibria. All the binary subsystems were studied prior to evaluating the predictive
capability of PC-SAFT toward the simultaneous chemical equilibria and phase equilibria. Overall,
PC-SAFT proved its excellent capabilities toward predicting chemical equilibrium composition in the
homogeneous composition range of the investigated systems as well as liquid–liquid phase behavior.
This study highlights the potential of a physical sound model to perform thermodynamic-based
modeling of chemical reacting systems undergoing liquid–liquid phase separation.
Keywords: liquid–liquid equilibrium; reaction equilibrium; thermodynamics; equation of state;
reactive separation
1. Introduction
The study of chemical reactions in multiphase systems is important from a purely sci-
entific point of view and becomes crucial in technical applications involving chemical and
phase equilibria (CPE) [1]. The presence of one or more chemical reactions adds internal
degrees of freedom (i.e., the species cannot only move between phases but also be con-
verted into different components) to the multicomponent system that must be considered
for designing chemical processes, thus increasing the intrinsic complexity of the system.
Even for kinetically controlled systems, CPE dictates the ultimate state of the system at the
given conditions (T, p, x) [2–4] since the molecules that take part in the reactive systems
(i.e., the reacting agents) ultimately decide on the position of the reaction equilibrium and
on the heterogeneity of the reaction system. Thermodynamic analysis, performed using
accurate thermodynamic models, represents a powerful tool to enable the estimation of
the reaction equilibrium (i.e., the maximum yield of a chemical reaction) and to assess the
possible demixing into two or more phases over the reaction coordinate. The integration of
chemical reaction and phase separation into one single unit, called reactive separation, has
several applications in the industry and in academia, e.g., reactive distillation [5–8], reactive
extraction [9–11], reactive crystallization [12,13] or reactive absorption [14–16]. Reactive
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Molecules 2023, 28, 1768 2 of 20

processes may offer several advantages over their non-reactive counterparts, such as an
increase in reaction yield and selectivity, the overcoming of thermodynamic restrictions
(e.g., azeotropes), energy saving or capital cost reduction [17–19]. Further, reactions in
multiple phases systems are encountered in living systems such as coacervates [20,21],
in downstream processes for biomolecules’ purification [22,23] or in geological fluid sys-
tems [24]. In process engineering, several methods have been developed so far to generate
feasible flowsheets for a given separation/reaction task or to dimension and optimize the
required unit operations [17], with all the proposed methods relying on the availability
of experimental data. While accurate thermodynamic and kinetic data are required for a
rigorous apparatus design, more qualitative data reflecting the thermodynamic behavior
of the system (such as the appearance of azeotropes or the presence of a heterogeneity
at given conditions, see for instance [25]) must be known at the early stage of project
development. In this sense, advanced thermodynamic models offer great potential for
cost and time saving since they allow existing experimental data to be correlated and their
values to be predicted at experimental conditions that were not investigated [26]. As well
as this correlative/extrapolative purpose, other properties that are difficult to measure
(such as the interface tension [27] or diffusion behavior [28]) can be estimated using a
thermodynamic model.
Motivated by the aforementioned importance, reactive phase equilibria have been the
subject of many scientific works, dealing with theory and/or with experimental studies.
Several authors focused on a pure theoretical–mathematical description of the reactive
phase equilibrium problem, ranging from exploring the conditions of uniqueness of the
phase equilibrium solution and the chemical equilibrium (CE) solution [29,30] or on its
properties [31–33] to the development of new mathematical formulations of the CPE
problem [34–40]. Doherty and coworkers [32,33,41,42] proposed the use of transformed
variables, a concept already developed in soviet literature [43,44], to represent reactive
phase diagrams and formulate working equations for CPE calculations. Later, they adapted
the transformed variable to concrete calculation problems, for instance, to phase stability
analysis [45] and the prediction of reactive azeotropes in a reactive mixture [46,47]. Several
algorithmic approaches to solve the combined CPE problem were developed [48–57]. One
successful approach is, for instance, the RAND method by Gautam et al., based on the work
of White et al. [58]. The RAND algorithm is nowadays employed in commercial software
such as Aspen Plus [59]. Recently, Koulocheris et al. [60] published an algorithmic approach
to perform CPE of reactive VLEs using traditional GE -models and tested their approach
to several systems containing azeotropes. For an extensive discussion on the different
available algorithms, we refer to the recent literature [53,61–63]. The group of Toikka
has worked extensively in the field of CPE with theoretical considerations [64–70] and
experimental/modeling contributions [71–76]. They have also published some extensive
reviews on existing data for CPE systems [1,67].
The purpose of the present work is to test the thermodynamic model Perturbed Chain
Statistical Associating Fluid Theory (PC-SAFT) for the modeling of CE in systems exhibiting
liquid–liquid equilibria (LLE) and to develop an algorithmic approach to perform this task.
PC-SAFT was chosen as it has already been used to model the CE in an esterification
system of 1-butanol with acetic acid by Grob et al. [77], and by Riechert et al. [78] to
model the reaction equilibrium in the esterification of ethanol and 1-propanol with acetic
acid. The electrolyte version ePC-SAFT was also successfully used to model the CE of
enzyme-catalyzed reactions [79,80], and the Michaelis constant [81–83], which can also
be interpreted as a reaction equilibrium between free and bounded enzyme. However,
none of these works considered the combined CPE problem. The proposed algorithm is
a stoichiometric, equation-solving method based on a double-nested procedure with a
successive update of the fugacity coefficients of all the components. The number of phases
and initial composition estimates are provided by the tangent plane stability analysis [84,85].
Although the general idea of the double-nested procedure is widely known (see, for
instance, [54,57,60,86–88]), in this work, we proposed some new ideas to improve the
Molecules 2023, 28, 1768 3 of 20

robustness of the CPE calculation. The algorithm was applied to predict the CPE of two
quaternary systems with an esterification reaction and the modeling results were compared
with experimental data from the literature. Section 2.1 provides a summary of the theory
of chemical reactions in multiphase equilibria, the different approaches to treat the CPE
and the consequences of the occurrence of chemical reactions on the topology of phase
diagrams. Details about the derivation and the structure of the proposed algorithm can
be found in Section 2.2. Sections 3.1–3.5 provide a description of the investigated systems
and the modeling strategy, as well as the calculated phase diagrams including the reaction
equilibria. Details about PC-SAFT are summarized in Appendix A.

2. Algorithmic Approach
2.1. Thermodynamics of Chemical Reactions and Multiple Liquid Phase Equilibria
For a system at
given temperature T, pressure p and respective total moles
n F = n1F , n2F , . . . , n FN of each components i = 1, . . . , N at an arbitrarily chosen feed
composition F, the mathematical solution of the CPE problem is defined by the number of
( j)
phases π and number of moles ni of each component i in each phase j that minimizes the
total Gibbs energy of the system (Equation (1)) [4,89]:

π N π
∑ ∑ ni ∑ n( j) T ·µ( j)
( j) ( j)
min
=
G= µi = (1)
n j =1 i =1 j =1

This is subject to the element conservation (Equation (2)), mass balance (Equation (3))
of each component, and non-negativity of the number of moles of each component
(Equation (4)) [90].
=
A·n F − b = 0 (2)
π
nF − ∑ n( j) = 0 (3)
j =1

( j)
ni ≥ 0 i = 1, . . . , N j = 1, . . . , π (4)
=
In Equation (2), A is the component–element matrix, which has dimension N E × N
(N E being the number of elements that build up the N components) and whose i-column
( a1i , a2i , . . . , a N E i )T contains the number of each element present in component i. The
N E -dimensional array b contains the number of moles of each element present in the
system (which remains unchanged). However, among the N E linear equations defined
=
by Equation (2), only N C ≤ N E equations, which are given by the rank of the matrix A,
=
N C = rank ( A), are sufficient to uniquely represent the condition of element conservation.
The difference N R = N E − N C is denoted number of key reactions in the literature.
Based on the employed strategy to solve the CPE problem, two classes of methods can
be distinguished, called non-stoichiometric and stoichiometric [38,90]. Non-stoichiometric
methods directly attempt at solving the optimization problem given by Equations (1)–(4),
using for instance the Kuhn–Tucker necessary conditions for minimization. Stoichiometric
methods avoid the element balance constraints (Equation (2)) by formulating the component
balance as a linear combination of N R reaction coordinates λ j , j = 1, . . . , N E according to
Equation (5) [60].

NR
=
niF = ni,0
F
+ ∑ νik ·λk i = 1, . . . , NnF = n0F + ν ·λ (5)
k =1
Molecules 2023, 28, 1768 4 of 20

Here, n0F is a set of molar fractions satisfying the elemental abundance condition
=
(Equation (2)) and ν being the stoichiometric matrix, which is a matrix of real numbers of
dimension N × N R satisfying the condition given by Equation (6) [90].
= = =
A· ν = 0 (6)
=
0 is a zero matrix of dimension N E × N R . Rules for the correct choice of the number
=
of key reactions N R and of the stoichiometric matrix ν is extensively discussed in the
literature [3,91] and will not be repeated here. From Equations (1), (3) and (5), the necessary
condition for the CPE can be derived, representing the condition that holds at equilibrium
and is expressed by Equations (7) and (8) [34].

(1) (2) (π )
µi = µi = . . . . = µi i = 1, . . . , N (7)
=
ν ·µ( R) = 0 (8)
where µ( R) represents the array of the chemical potentials of all the components in one cho-
sen reference phase. Equation (8) is equivalent to the analogue reformulation based on the
activity-based equilibrium constant, which is written for a reaction k in Equation (9) [2,90].

N N
( R) ( R) νik
 
∑ νik ·µi = ∆ R gk0 + RT ∑ ln xi γi
( R)
=0 (9)
i =1 i =1

∆ R gk0 is the standard Gibbs energy of reaction. Equation (9) summarizes the well-
known expression of the activity-based equilibrium constant Ka,k given by
Equation (10) [2,90].
!
∆ R gk0 N 
( R) ( R) νik

= ∏ x i γi
( R) ( R)
Ka,k = exp − Ka,k = Kx,k Kγ,k (10)
RT i =1

The previous conditions (Equations (7) and (8)), together with the mass balance
(Equations (4) and (5)) build up a system of π · N + N R equations that must be solved on
π · N + N R variables (which are the π · N non-negative number of moles if each component
in each phase and N R reaction coordinates). Equations (7) and (8) build the necessary
equilibrium condition of an N-component multiphase system with NR key reactions. It
must be pointed out that there could be more solutions of Equations (7) and (8) for a
different number or even for the correct number of phases π (for instance, at the trivial
solution or when an LL solution is present above the boiling point of the mixture) since the
described condition is necessary but not sufficient.
For the determination of the equilibrium constant Ka of a chemical reaction, two
approaches can be employed: the first is to estimate the standard Gibbs energy of reaction
∆ R gk0 from the standard energy of formation ∆ F gi0 of each component i in a chosen reference
state. The second approach relies on the availability of at least one experimental equilibrium
composition x ∗,exp and of a thermodynamic model to predict the set of activity coefficients
γ( T, p, x ∗,exp ), which can then be used to determine the Ka,k based on Equation (10).
In a system with chemical reactions, the number of degrees of freedom F according to
the Gibbs phase rule involving π phases and N components is reduced by the number of
key reactions NR , according to Equation (11) [64,92].

F = 2 − π + N − NR (11)

The consequences of chemical reactions in a multiphase system for the resulting phase
diagrams have been discussed extensively, for instance, in previous publications of the
Toikka group [64–66]. Each key reaction decreases by one the dimension of the allowable
composition space that can be reached by the system at equilibrium. For example, in a
Molecules 2023, 28, 1768 5 of 20

ternary homogeneous system with a key reaction of the form A + B C at constant T and
p, the number of degrees of freedom is F = 2 − 1 + 3 − 1 − 2 = 1. That is, the dimension
of the composition space is reduced from two (non-reactive) to one (reactive), and thus,
all the equilibrium compositions will belong to a line, called chemical equilibrium curve
(CE curve) [64]. The corresponding equilibrium composition of a quaternary system with
one reaction A + B C + D will span a chemical equilibrium surface (CE surface) [64]. A
manifold of CE curves for different values of the equilibrium constant Ka in a ternary ideal
system are given in the ternary diagram of Figure 1.
If the system under consideration shows high non-ideality up to miscibility gap, some
Molecules 2023, 28, x FOR PEER REVIEW 5 of 20
of the curves of the manifold can show a strong deviation from the ideal hyperbolic form
shown in Figure 1. Othmer et al. [30] showed that for strongly non-ideal systems, up to
three solutions can be present for some curves, although only one or two (belonging to
and p, the number of degrees of freedom is 𝐹 2 1 3 1 2 1. That is, the dimen‐
asion
tie-line)
of thecorresponds to the
composition space stable solution.
is reduced from two Figure 2 shows
(non‐reactive) some
to one CE curves,
(reactive), and calculated
for theallsame
thus, reaction A
the equilibrium +B
compositionsC as ofbelong
will Figureto1,a line,
crossing
calledthe miscibility
chemical gap of a strongly
equilibrium
non-ideal system.
curve (CE curve) Calculations
[64]. are performed
The corresponding equilibriumusing the algorithm
composition developed
of a quaternary systemin Section 2.2.
withtie-line
The one reaction 𝐴 𝐵 ⇌ 𝐶 two
that connects 𝐷 will spanata CE
points chemical equilibrium
is called surface
a reactive (CE surface)
tie-line [32], with a further
[64]. A manifold of CE curves for different values of the equilibrium
distinction of a unique reactive tie-line if it appears in a ternary system constant 𝐾 in[1,32,64].
a ter‐
nary ideal system are given in the ternary diagram of Figure 1.

Figure 1.
Figure 1. CE
CEcurves
curvesforfor
different values
different of theof
values CEthe
constant Ka in a ternary
CE constant Ka in system 𝐴 system
a ternary 𝐵 ⇌ 𝐶 that
A+B C that
assumes ideal mixing behavior (Kγ = 1 in Equation (10)).
Molecules 2023, 28, x FOR PEER REVIEW 6 of 20
assumes ideal mixing behavior (Kγ = 1 in Equation (10)).
If the system under consideration shows high non‐ideality up to miscibility gap,
some of the curves of the manifold can show a strong deviation from the ideal hyperbolic
form shown in Figure 1. Othmer et al. [30] showed that for strongly non‐ideal systems, up
to three solutions can be present for some curves, although only one or two (belonging to
a tie‐line) corresponds to the stable solution. Figure 2 shows some CE curves, calculated
for the same reaction 𝐴 𝐵 ⇌ 𝐶 as of Figure 1, crossing the miscibility gap of a strongly
non‐ideal system. Calculations are performed using the algorithm developed in Section
2.2. The tie‐line that connects two points at CE is called a reactive tie‐line [32], with a fur‐
ther distinction of a unique reactive tie‐line if it appears in a ternary system [1,32,64].

Figure 2. Hypothetical CE curves for different values of the CE constant Ka in a strongly non‐ideal
Figure 2. Hypothetical CE curves for different values of the CE constant Ka inPC‐SAFT
ternary system 𝐴 𝐵 ⇌ 𝐶 with a miscibility gap. Calculations were performed using
a strongly non-ideal
ternary
with thesystem A+
algorithm B C in
developed with a miscibility
Section gap. Calculations
2.2 and parameters were3.2.
listed in Section performed using PC-SAFT with
the algorithm developed in Section 2.2 and parameters listed in Section 3.2.
Whether or not phase split occurs in the reaction system is dictated by the properties
of the pure components and of the mixture. The kind of molecules involved in the reaction
mixture determine the equilibrium constant Ka, which in turn dictates if the reaction path
undergoes phase split(s). The ternary diagram (Figure 2) shows one CE curve passing
through the homogeneous region (Ka = 1.8), three crossing the two‐phase region one time
Molecules 2023, 28, 1768 6 of 20
Figure 2. Hypothetical CE curves for different values of the CE constant Ka in a strongly non‐ideal
ternary system 𝐴 𝐵 ⇌ 𝐶 with a miscibility gap. Calculations were performed using PC‐SAFT
with the algorithm developed in Section 2.2 and parameters listed in Section 3.2.
Whether or not phase split occurs in the reaction system is dictated by the properties
of theWhether
pure components
or not phaseand of the
split mixture.
occurs in the The kindsystem
reaction of molecules involved
is dictated by the in the reaction
properties
mixture determine
of the pure componentsthe equilibrium constant
and of the mixture. TheKkind
a , which in turn dictates
of molecules involvedifin the
thereaction
reactionpath
undergoes phase split(s).
mixture determine The ternary
the equilibrium diagram
constant Ka, which(Figure 2) dictates
in turn shows one if theCE curvepath
reaction passing
undergoes
through the phase split(s). The
homogeneous ternary
region (Ka =diagram
1.8), three(Figure 2) shows
crossing one CE curve
the two-phase regionpassing
one time
through
(one, the homogeneous
however, showing one region (Ka =point
tangent 1.8), three
to the crossing
binodal themore
two‐phase region one
than crossing it) time
and one
crossing the two-phase region twice (Ka = 2.25). The composition points inside the one
(one, however, showing one tangent point to the binodal more than crossing it) and binodal
crossing
will the two‐phase
not exist in a systemregion twice (Ka =and
in equilibrium 2.25). The
will composition
split points inside
into two phases (giventhebybinodal
two points
will not exist
connected by in a system in
a tie-line). equilibrium
However, the and will split
crossing intoof
points two
CEphases
curve (given by two represents
and binodal points
connected by a tie‐line). However, the crossing points of CE curve and
points belongs to the reactive tie-lines. An exemplary diagram of a reactive system with binodal represents
points
two belongs
reactive to the is
tie-lines reactive
showntie‐lines.
in FigureAn3,exemplary
representing diagram of asolution
the real reactive ofsystem with in
the system
two reactive tie‐lines
Figure 2 with Ka = 2.25. is shown in Figure 3, representing the real solution of the system in
Figure 2 with Ka = 2.25.

Figure 3. Resulting phase diagram of the hypothetical non-ideal ternary system A + B C from
Figure 2 for Ka = 2.25. Visible are the two disconnected CE curves passing through the homogeneous
phase and the two unique reactive tie-lines I and II.

2.2. Algorithm Architecture

In this section, our implementation of the algorithm to perform numerical calculation
of the CPE is presented. Although the implementation is general, i.e., not limited to a single
key reaction and neutral components (see, for instance, our previous work [93,94]), its scope
in this work is to calculate the coupled reaction equilibrium and LLE of the two investigated
esterification systems. Thus, only systems containing four molecular (i.e., non-charged)
components and described by one key reaction are considered.
The phase equilibrium calculation starts with a given number of phases and an
initial guess composition, which in our approach is provided by the tangent plan stability
F = x F ). The number of
analysis [84,85]. Initially, a unimolar feed amount is initialized (ni,0 i,0
moles of each component in each phase is thus given by Equation (12).

( j) ( j) ( j)
ni,0 = xi,0 α0 (12)
Molecules 2023, 28, 1768 7 of 20

Instead of searching for a direct solution of Equation (7), the objective function is
reformulated as given by Equation (13) for each component.

( j) i = 1, . . . , Nneut
xi n
( j) ( Ri )
o
1− (R )
exp ln ϕ i − ln ϕ i = 0 j = 1, . . . , π ; j 6= Ri (13)
i
xi

( j)
In Equation (13), ϕi is the fugacity coefficient of component i in phase (j) and Ri
n o
( j) (R )
represents a reference phase, which is chosen for component i. Thus, exp ln ϕi − ln ϕi i
represents the partition coefficient of component i between phase j and the reference phase
Ri . For a reactive system with N R key reactions, N R further equations must be formulated,
representing the CE condition given by Equation (8). In our work, the N R objective
functions are reformulated by Equation (14).

( R) ( R)
Kγ,m Kx,m
1− =0 (14)
Ka,m

( R)
The superscript (R) in Equation (14) means that the activity coefficients in Kγ,m and
( R)
the concentrations in Kx,m refer to the component in only one reference phase (which do
not have to be necessarily the same for all the components). Equation (13) builds up a
set of (π − 1)· N equations, and if N R key reactions must be defined, the total number of
equations becomes (π − 1)· N + N R .
Thus, the roots of the system of equations given by Equations (13) and (14) can be found
by changing the value of (π − 1)· N + N R variables. For each component i, a reference
phase Ri is defined, which at the same time is used to impose the isofugacity criterion by
Equation (13). The reference phase of each component is chosen as the phase in which the
highest initial number of moles of component i (according to Equation (11)) is present at
the beginning of the CPE calculation. The number of moles of each component i in the
respective reference phase Ri is found by mass balance by imposing that the total number
of moles must be equal to the number of moles of the feed (as given by Equation (3)). If
N R key reaction must be defined, then the total feed composition is corrected using the
stoichiometric coefficients and N R reaction coordinates, which are varied by the algorithm
as well. The implemented equation for the number of moles of each component in its
reference phase is given by Equation (15).
!
NR π
∑ ∑
( R) (m) ( j)
ni = niF − νi λm − ni (15)
m =1 j=1
j 6= R

( j)
Thus, (π − 1)· N + N R variables ((π − 1)· N number of moles ni of each component
and N R reaction coordinates λm , m = 1, . . . , N R ) are varied to find the root of the system of
(π − 1)· N + N R equations given by Equations (13) and (14).
As noted by other authors, the computationally most expensive step in phase equi-
librium calculation is the evaluation of the fugacity coefficients in Equations (13) and (14)
[54,87,88]. Boston et al. [87] suggested to solve the working equations in an inner loop using
constant values of the fugacity coefficients and to update them, after convergence, in an
outer loop. The iteration was performed until the relative difference between two successive
solutions fell below a certain value. Upon using this method in our algorithm, we found
convergence for the investigated esterification systems in this study. However, we observed
oscillation and ultimately divergence when treating systems of concentrated electrolytes,
high-pressure VLE with supercritical components and concentrated polymer solutions. In
order to guarantee general robustness, we modified the double-nested approach. Instead
Molecules 2023, 28, 1768 8 of 20

of working with constant fugacity coefficients in the inner loop, we approximated them as
linear functions of the compositions using partial derivatives, as given by Equation (16).

N ( j)
    ∂ ln ϕi  ( j) ( j) i = 1, . . . , N

∑ ∂xk
( j) ( j) ( j)
ln ϕi T, p, x ( j) = ln ϕi T, p, x0 + x k,0 − x k (16)
k =1
j = 1, . . . , π

The partial derivatives of the fugacity coefficients in Equation (16) were evaluated
numerically by finite difference at the beginning of the calculation, and then updated
from the previous values using a Broyden estimation [95] after each calculation step.
The resulting non-linear system of equations was solved using a Newton algorithm with
variable step length α (Equation (17)).

= −1


X k +1 = X k − α · J Xk ·F Xk (17)

In Equation (17), X represents the array of (π − 1)· N + N R variables, F Xk represents the

=

array of objective functions (Equations (13) and (14)) calculated at the point Xk and J Xk is the
respective Jacobian matrix. The partial derivatives in the Jacobian matrix are calculated via auto-
matic differentiation using dual numbers [96]. The step length α is reduced if the new estimate
Xk+1 leads to one or more negative concentrations,
or if the

norm of the new objective function
array is greater than the previous (i.e., if F Xk+1 > F Xk ). After convergence of Equations (13)
and (14), the value of the fugacity coefficients and their derivatives in Equation (16) is updated
and the iteration of Equation (17) is started again. The double-nested procedure is repeated
until the change in the calculated mole numbers between two updates falls below a tolerance
δtol = 10−8.

Algorithmic Structure
In following, the calculation procedure is shown using the hypothetical mixture of
Figures 2 and 3 as test systems. These systems serve also as a first validation of our
approach, since they show characteristic topologies of reactive phase diagrams already
reported in the literature [30,66]. In sum, the algorithmic procedure to perform a reactive
flash calculation according to our strategy consists of the following steps:
1- First the feed composition x F , the temperature p and the pressure T is given. Initially,
an homogeneous CE calculation is performed at these conditions, according to the
stoichiometry of the defined key reactions N R . This is equivalent to moving the compo-
sition point, along a trajectory imposed by the stoichiometry called stoichiometry line,
to the (hyper-)surface (composition x F0 ) where the CE condition for each key reaction
is fulfilled (Equation (8)). For a simple reaction A + B C and the corresponding
ternary phase diagram, this chemical equilibration step can be visualized in Figure 4.
2- Secondly, phase stability analysis according to the (non-reactive) tangent plane dis-
tance function [84,85] is performed for the chemically equilibrated feed. If the equili-
brated feed lies inside the miscibility gap, two estimates of both liquid phase concen-
trations are provided (Figure 5).
3- Third, CE is performed for each of the single phases provided by step 2. This is
equivalent to moving each single phase, according to the reaction stoichiometry, to
the chemical equilibrium (hyper-)surface. The overall feed composition will move as
well; however, it will in general not lie to the chemical equilibrium (hyper-)surface as
with the single phases. This third step will finally provide good initial point for the
final reactive flash calculation.
4- Finally, rigorous reactive flash calculation according to the strategy proposed in the
last section is applied. After final convergence, two equilibrium points that satisfy
Equations (7) and (8) are returned (Figure 6).
 3‐
Molecules 2023, 28, x FOR PEER REVIEWThird, CE is performed for each of the single phases provided by step9 2. of This
20 is equiv‐
alent to moving each single phase, according to the reaction stoichiometry, to the
chemical equilibrium (hyper‐)surface. The overall feed composition will move as
well; however,
2‐ Secondly, it will analysis
phase stability in general not lietoto
according thethe chemical equilibrium
(non‐reactive) tangent plane(hyper‐)surface
dis‐
as with
tance the single
function phases.
[84,85] is Thisforthird
performed step willequilibrated
the chemically finally provide
feed. Ifgood initial point for
the equili‐
the final
brated feedreactive flash
lies inside calculation.
the miscibility gap, two estimates of both liquid phase concen‐
Molecules 2023, 28, 1768 4‐ trations
Finally,arerigorous
providedreactive
(Figure 5).
flash calculation according to the strategy proposed in the 9 of 20
3‐ Third, CE is performed
last section is applied.for each of the
After finalsingle phases provided
convergence, two by step 2. This ispoints
equilibrium equiv‐ that satisfy
alent to moving each single phase, according to the reaction stoichiometry, to the
Equations (7) and (8) are returned (Figure 6).
chemical equilibrium (hyper‐)surface. The overall feed composition will move as
well; however, it will in general not lie to the chemical equilibrium (hyper‐)surface
as with the single phases. This third step will finally provide good initial point for
the final reactive flash calculation.
4‐ Finally, rigorous reactive flash calculation according to the strategy proposed in the
last section is applied. After final convergence, two equilibrium points that satisfy
Equations (7) and (8) are returned (Figure 6).

Figure 4. The initial feed point 𝑥̅ is moved along a stoichiometry line to the CE curve (green line).
Figure 4. Thesystem
In the depicted initialthefeed
finalpoint x F is 𝑥̅moved
composition along
lies inside theamiscibility
stoichiometry
gap (greyline area)tofor
the
theCE curve (green line). In
the depicted
chosen system
initial feed the final composition x F0 lies inside the miscibility gap (grey area) for the chosen
composition.

initial
Figure 4.feed composition.
The initial feed point 𝑥̅ is moved along a stoichiometry line to the CE curve (green line).
In the depicted system the final composition 𝑥̅ lies inside the miscibility gap (grey area) for the
chosen initial feed composition.

Figure 5. After reaching the CE curve, phase stability is performed

Molecules 2023, 28, x FOR PEER REVIEW 10 of 20 for the chemical equilibrated feed

x F0 . The tangent plane criterion is implemented in this work, which provides estimate of the phase
compositions (grey
Figure 5. After reaching the points) if instability
CE curve, phase of the liquid
stability is performed phaseequilibrated
for the chemical is detected.
feed 𝑥̅ . The tangent plane criterion is implemented in this work, which provides estimate of the
phase compositions (grey points) if instability of the liquid phase is detected.

Figure 6. After convergence of the CPE calculation, the concentration of the two phases 𝑥̅ and 𝑥̅
Figure
belonging 6. After
to the same convergence of the
tie‐line and the chemical CPE calculation,
equilibrium the
curve (the so‐called concentration
“unique reactive of the two phases x 0 and x 00
tie‐line”) is found. The resulting feed composition still remains on the stoichiometric line (NOT on
belonging to the same
the chemical equilibrium line). tie-line and the chemical equilibrium curve (the so-called “unique reactive
tie-line”) is found. The resulting feed composition still remains on the stoichiometric line (NOT on
Figure 7 summarizes, in a flowchart, the computational steps of the CPE procedure
the chemical
explained equilibrium
in this section and their line).
calling order within the implemented algorithm.
 Figure 6. After convergence of the CPE calculation, the concentration of the two phases 𝑥̅ and 𝑥̅
Molecules 2023, 28, 1768 belonging to the same tie‐line and the chemical equilibrium curve (the so‐called “unique reactive10 of 20
tie‐line”) is found. The resulting feed composition still remains on the stoichiometric line (NOT on
the chemical equilibrium line).

Figure 7 summarizes, in a flowchart, the computational steps of the CPE procedure

Figure 7 summarizes, in a flowchart, the computational steps of the CPE procedure
explained inthis
explained in thissection
sectionand
and their
their calling
calling order
order within
within the the implemented
implemented algorithm.
algorithm.

Figure 7. Flowchart that illustrates the computational steps of the CPE procedure implemented in the
proposed algorithm. z* denotes a chemical equilibrated, homogeneous feed (relevant for a feed lying
outside the miscibility gap), and x(1,est) and x(2,est) denote composition estimates of the heterogeneous
feed after the phase stability test.

3. Results
3.1. The Reaction Systems Considered in This Work
In this work, two esterification systems were considered to test our approach and the
performance of PC-SAFT to predict, simultaneously, the occurrence of LLE along the CE.
Those are the quaternary system acetic acid + 1-pentanol + pentyl acetate + water (system 1)
and the system acetic acid + 1-hexanol + hexyl acetate + water (system 2) according to the
chemical Equations (18) and (19).

CH3 COOH + C5 H11 OH CH3 COOC5 H11 + H2 O (18)

CH3 COOH + C6 H13 OH CH3 COOC6 H13 + H2 O (19)

The first system was characterized by Senina et al. [72] at T = 318.15 K and p = 1.013 bar,
the second system was extensively studied by Schmitt et al. [97–99] in a larger temperature
range (293.15–403.15K with special focus on the range 353.15–393.15K) at p = 1.013 bar.
Within the investigated temperature and pressure range, all the binary subsystems given
by the alcohols and respective acetate esters with water show partial miscibility [100,101].
Thus, both the quaternary and all the ternary subsystems show a miscibility gap [98,102,103];
the only exception is the homogenous system acetic acid + alcohol (1-pentanol or 1-hexanol)
+ ester (pentyl acetate or hexyl acetate). Esterification is a catalytic process and is practically
frozen without a catalyst [72]: Schmitt [97] investigated the autocatalytic esterification
of 1-hexanol with acetic acid at 298.15 K, showing that the reaction did not approach
the equilibrium even after weeks. The reaction can be carried out in the presence of an
Molecules 2023, 28, 1768 11 of 20

inorganic acid (homogeneous catalysis) or using a solid catalyst (heterogeneous cataly-

sis). Senina et al. [72] used HClaq in concentrations less than 2 wt%, whereas Schmitt [97]
employed an ion-exchange resin (Amberlyst CSP2). Due to the relatively low catalyst
concentration, the catalyst was not considered in our calculations since it only marginally
affects the phase equilibrium. In both works [72,97], the measurement of the final equilib-
rium composition (homogeneous CE, LLE or simultaneous CE and LLE) was carried out
via gas chromatography.

3.2. PC-SAFT Parameters for the Considered Reaction Systems

In order to model the subsystems of the esterification systems (18) and (19), the
parameters of the applied model must be determined. All the pure-component PC-SAFT
parameters used in this work were retrieved from the literature and are listed in Table 1.
Table 1. PC-SAFT pure-component parameters used in this work to model the CE and LLE in the
investigated systems.

seg
Component mi /− σi / ui kB−1 /K Ni εAi Bi kB−1 /K κAi Bi /- Ref.
Water 1.2047 * 353.95 2 2425.7 0.04509 [104]
Acetic acid 1.3402 3.8582 311.59 2 3044.4 0.07555 [105]
1-Pentanol 3.6260 3.4508 247.28 2 2252.1 0.01033 [105]
1-Hexanol 3.5146 3.6735 262.32 2 2538.9 0.00575 [105]
Pentyl Acetate 4.7077 3.4729 234.57 2 0.0 0.04509 [106]
Hexyl Acetate 4.8847 3.5834 241.42 2 0.0 0.04509 [107]
10.11e−0.01775 T − 1.417e−0.01146 T


∗σ = 2.7927 +

The binary interaction parameters used in this work were in part retrieved from the
literature and, if not available, were regressed from mixture properties (LLE data in binary
or ternary systems and VLE data in binary systems, see Table 2).

Table 2. Binary interaction parameters used in this work to model multicomponent mixtures using
PC-SAFT. Definition of the kij values according to the Appendix A.

Property Used for

Component 1 Component 2 kij,298.15 /- kij,T /K Ref.
Estimation
Water Acetic acid −0.1247 - VLE-binary [107]
Water 1-Pentanol 0.001604 0.00016 LLE-binary [108]
Water Pentyl Acetate −0.0228 - LLE-binary This work (using data from [100])
Water 1-Hexanol 0.010105 0.000404 LLE-binary [108]
Water Hexyl Acetate −0.01 0.0015 LLE-binary This work (using data from [100])
Acetic acid 1-Pentanol −0.1 - LLE-ternary This work (using data from [103])
Acetic acid 1-Hexanol −0.033 - LLE-ternary This work (using data from [103])
Acetic acid Pentyl Acetate −0.1 - LLE-ternary This work (using data from [102])
Acetic acid Hexyl Acetate −0.08 −0.0004 LLE-ternary This work (using data from [98])
1-Pentanol Pentyl Acetate −0.0095 - VLE-binary This work (using data from [109])
1-Hexanol Hexyl Acetate −0.0042 - VLE-binary This work (using data from [98])

For the calculation of the CE curves in Figures 2 and 3, pure-component parameters

listed in Table 3 were used. The hypothetical components are called A, B, C, as used in the
calculated ternary diagrams, and the used hypothetical binary interaction parameters were
chosen to: k AB = −0.045, k BC = −0.025, k AC = 0.045.
Molecules 2023, 28, 1768 12 of 20

Table 3. PC-SAFT pure-component parameters of hypothetical mixture A+B+C used to calculate the
exemplary CE curves in Figures 2 and 3.
seg −1 −1
Component mi /− σi /Å ui kB /K Ni εAi Bi kB /K κAi Bi /-
A 2.4000 3.2000 200.00 2 2500.0 0.05
B 1.0800 3.0000 400.00 2 2500.0 0.05
C 2.8000 3.8000 280.00 0 - -

3.3. The Reaction Equilibrium Constants Ka of the Considered Chemical Reactions

For the determination of the equilibrium constant Ka of both chemical reactions
(Equations (18) and (19)), we used one experimental equilibrium composition x ∗,exp and
predicted a set of activity coefficients γ( T, p, x ∗,exp ) using PC-SAFT and the parameters
applied in Tables 1 and 2. This was then used to determine the Ka,k based on Equation (10).
This method circumvents the approximations made in the estimation of the standard energy
of formations. Senina et al. [72] measured the CE composition in the homogeneous region
of system 1 as well as nine quaternary tie-lines at the CE at the given T and p conditions.
Other experimental data [110,111] were determined in the homogeneous liquid phase
but at saturation condition, i.e., along the condition of liquid–vapor coexistence. Since
T and p at saturation vary continuously with composition, only the data of Senina et al.
(determined at fixed T and p) were considered in this work. For the same reasons, only CE
compositions at fixed T and p, determined by Schmitt et al. [97], were considered in this
work for the determination of Ka in system 2. The resulting Ka values determined based on
the experimental data from the literature are listed in Table 4.

Table 4. Obtained Ka values for both systems 1 and 2, as well as the respective conditions (T and p)
and the according references for the experimental equilibrium compositions.

System T/K p/bar Ka / − Ref. (for the Data)

1 318.15 1 43.99 [72]
2 353.6 1 22.92 [97]

3.4. Prediction Results of the CPE Problem for Both Reactions under Study
Figures 8 and 9 show the CE surface in the composition tetrahedron of both systems,
including the heterogeneous region of CE (“unique chemical reactive surface”, according
to [72]). These results were obtained using our
Molecules 2023, 28, x FOR PEER REVIEW
developed algorithm (Section 2.2) fed by
13 of 20
PC-SAFT (see the Appendix A) and the used parameters (Tables 1 and 2) for the activity
coefficients
to [72]). These results as
werewell
obtained asusing
theourequilibrium
developed algorithm constants (Table 4). Both, the reaction surface (CE
(Section 2.2) fed by
surface)
PC‐SAFT (see theand the
Appendix liquid–liquid
A) and the used parameters miscibility
(Tables 1 and 2) for gap (binodal
the activity
coefficients as well as the equilibrium constants (Table 4). Both, the reaction surface (CE
curve) were predicted in good
agreement
surface) with the
and the liquid–liquid experimental
miscibility data.
gap (binodal curve) were predicted in good
agreement with the experimental data.

Figure 8. Quaternary phase diagram of system 2 (Equation (19)) at 353.6 K and 1 bar showing the
Figure 8. Quaternary phase diagram of system 2 (Equation (19)) at 353.6 K and 1 bar showing the
PC‐SAFT‐predicted CE surface (green surface) and the PC‐SAFT‐predicted binodal (black curve en‐
compassing the grey area). Experimental CE compositions of Schmitt et al. [97] are represented as
PC-SAFT-predicted CE surface (green surface) and the PC-SAFT-predicted binodal (black curve
grey spheres. All PC‐SAFT predictions using parameters in Tables 1 and 2.

encompassing the grey area). Experimental CE compositions of Schmitt et al. [97] are represented as
grey spheres. All PC-SAFT predictions using parameters in Tables 1 and 2.
 Figure 8. Quaternary phase diagram of system 2 (Equation (19)) at 353.6 K and 1 bar showing the
Molecules 2023, 28, 1768 PC‐SAFT‐predicted CE surface (green surface) and the PC‐SAFT‐predicted binodal (black curve en‐13 of 20
compassing the grey area). Experimental CE compositions of Schmitt et al. [97] are represented as
grey spheres. All PC‐SAFT predictions using parameters in Tables 1 and 2.

Quaternary
Figure9.9.Quaternary
Figure phase
phase diagrams
diagrams of system
of system 1 (Equation
1 (Equation (18))(18)) at 318.15
at 318.15 K andK1and 1 bar showing
bar showing the the
PC-SAFT-predictedCE
PC‐SAFT‐predicted CEsurface
surface(green
(greensurface)
surface) and
and thethe calculated
calculated binodal
binodal (black
(black curve
curve encompassing
encompass‐
ing
thethe grey
grey area).Left:
area). Left: Experimental
Experimental CE CEcompositions
compositions of of
Senina
Seninaet al.
et [72] (grey(grey
al. [72] spheres). Right: Right:
spheres).
Experimental tie‐lines [72] (black spheres connected by a dashed line) and PC‐SAFT‐predicted
Experimental tie-lines [72] (black spheres connected by a dashed line) and PC-SAFT-predicted tie‐
lines (grey spheres connected by a solid line). All PC‐SAFT predictions using parameters in Tables
tie-lines (grey spheres connected by a solid line). All PC-SAFT predictions using parameters in
1 and 2.
Tables 1 and 2.
3.5.
3.5.Discussion
Discussion
Figures 8 and 9 show that the CE composition is predicted quantitatively correct by
Figures 8 and 9 show that the CE composition is predicted quantitatively correct by PC-
PC‐SAFT, for both systems at the investigated T and p conditions, and in the whole com‐
SAFT, for both systems at the investigated T and p conditions, and in the whole composition
position range. System 2 shows a much broader miscibility gap in the CE surface than
range. System 2 shows a much broader miscibility gap in the CE surface than system 1, even
at a higher temperature (353.6 K, compared to 318.15 K of system 1). This is in accordance
with the subsystems, i.e., the much greater miscibility gap of 1-hexanol and hexyl acetate
with water compared to their homologues 1-pentanol and pentyl acetate. The absence of
experimental data of the CE tie-lines for system 2 did not allow for a direct comparison
with the two-phase CPE prediction results in this system. Experimental CE tie-lines are
available for system 1, and thus they were compared with the PC-SAFT predictions. The
predicted CE tie-lines show qualitative agreement with the experimental data. It can be
observed from Figure 9 that deviations between PC-SAFT and the experiments occur when
acetic acid is present in the system. This inaccurate behavior of PC-SAFT at high acetic
acid concentrations is already knows from previous work [77] and is probably due to the
lack of representation of the dimerization behavior of acetic acid and the cross-association
with the other components present in the mixture. A more detailed investigation of phase
equilibria with acetic acid should be carried out in the future, trying to better capture
the real association behavior of acetic acid in complex mixtures. This may require the
investigation of the more refined (and likely more phenomenological) parametrization
strategies of acetic acid and binary mixtures containing acetic acid.
Nevertheless, in sum, it can be concluded that the mathematical algorithm that has
been developed in this work allows a satisfying estimation of chemical equilibria as well as
liquid–liquid phase separation in the chemical reaction space by using PC-SAFT as the input
tool for the activity coefficients. The results shown for the CE and CPE of the quaternary
esterification systems are pure predictions since the model was parametrized using only
pure-component vapor pressure and density (to determine the pure-component parameters,
see Table 1) as well as the VLE and LLE of the binary and ternary subsystems (to determine
the binary interaction parameters in Equation (A5), see Table 2). This is an important
contribution to the design of reactive systems that may undergo phase separation.

4. Conclusions
In this work, an algorithm was successfully designed and implemented to predict
CPE in multiphase multicomponent systems. New ideas were proposed to improve the
Molecules 2023, 28, 1768 14 of 20

robustness of the calculation procedure when calculating the CPE of strongly non-ideal
systems. The algorithm uses PC-SAFT to describe the thermodynamic behavior of the
system, i.e., the fugacity coefficients of the reacting agents. Prior to modeling, the related
literature on the thermodynamics of multiphase reactive systems was reviewed, and the
proposed algorithm was tested against a hypothetical ternary mixture with a chemical
reaction, showing that the topologies of reactive phase diagrams that are reported in the
literature are also predicted well by our approach. Using the implemented algorithm, the
predictive capability of PC-SAFT on the CPE could be tested successfully for the first time,
against the simultaneous CE and LLE in two quaternary esterification systems, formed
respectively by esterification of acetic acid and 1-pentanol and of acetic acid and 1-hexanol.
The CE composition in the homogeneous phase were predicted quantitatively correct by
PC-SAFT in both systems and over the whole composition range and the investigated T
and p condition. The prediction of simultaneous CE and LLE was qualitatively correct in
the whole composition range, showing higher deviations from experimental data in the
presence of acetic acid. This study suggests potential improvements, possibly in a new
parametrization strategy for pure and binary mixtures of acetic acid, but more importantly
suggests the use of PC-SAFT to design reactive systems that may undergo phase separation.

Author Contributions: Conceptualization, M.A.; methodology, M.A.; software, M.A. and C.H.;
validation, M.A.; formal analysis, M.A.; investigation, M.A.; resources, G.S. and C.H.; data curation,
M.A.; writing—original draft preparation, M.A.; writing—review and editing, C.H.; visualization,
M.A.; supervision, G.S. and C.H.; project administration, G.S. and C.H.; funding acquisition, G.S. and
C.H. All authors have read and agreed to the published version of the manuscript.
Funding: The authors acknowledge funding from the Deutsche Forschungsgemeinschaft (DFG,
German Research Foundation) under Germany’s Excellence Strategy–EXC 2033–project number
390677874. Translation into German required: “Gefördert durch die Deutsche Forschungsgemein-
schaft (DFG) im Rahmen der Exzellenzstrategie des Bundes und der Länder–EXC 2033–Projektnummer
390677874–RESOLV”.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: The data supporting the reported results are all given in this manuscript
and in Appendix A.
Acknowledgments: The authors acknowledge the work of Rinesh Vennoli.
Conflicts of Interest: The funders had no role in the design of the study; in the collection, analyses,
or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Appendix A. PC-SAFT
PC-SAFT is a thermodynamic model belonging to the SAFT-type equations of state,
and it was developed by Groß and Sadowski in 2001 [105,112]. As with all the SAFT-like
equations of state, PC-SAFT bases its description of intermolecular forces on the formalism
of perturbation theory [113], which allows an exact separation of each contribution of the
N-body intermolecular potential UN into two (or more) contributions in the final expression
of the residual Helmholtz energy Ares (Equation (A1)).

(0) (1)
UN = UN + UN (A1)

For a spherical symmetric fluid, the potential separation given in Equation (A1)
translates (exactly) into the residual Helmholtz energy as given by Equation (A2).

(1)
!
res (0) U
A = −k B T ln ZN = −k B T ln ZN hexp − N i 0 = A (0) + A (1) (A2)
kB T
Molecules 2023, 28, 1768 15 of 20

(0)
In Equation (A2), ZN denotes the configurational integral of the unperturbed system
and 0 indicates a canonical average in the unperturbed system [114]. From Equation (A2),
the residual Helmholtz energy can be written as the sum of a different contribution. Within
this work only three terms, the hard chain, the dispersion and the association contributions,
are considered to model the investigated systems (Equation (A3)).

Ares  
ares = = a HS + aCh, f or + a Disp + a Assoc (A3)
Nk B T

In Equation (A3), a HS denotes the hard-sphere contribution described using the

Carnahan–Starling equation for a mixture of hard spheres, aCh, f or is the contribution due to
chain formation from unconnected hard-sphered described by the Wertheim association
theory [115–118], a Disp is the contribution of short-ranged, anisotropy dispersion forces
developed by Groß and Sadowski [112] and a Assoc is the contribution due to strong, short-
ranged and highly isotropic forces (such as hydrogen bonds) described by the Wertheim
association theory as well. The term in brackets denotes the contribution of the hard-chain
reference fluid a HC = a HS + aCh, f or over which the dispersion contribution is developed.
The main difference between PC-SAFT and the other SAFT-based equations of state is the
choice of the reference fluid to develop the dispersion term a Disp according to Equation
(A2), which is the hard-chain fluid for PC-SAFT. Therefore, information about the deviation
from the symmetrical, spherical shape in real molecules is accounted for in the dispersion
term. The association term a Assoc , on the other hand, is developed as a perturbation of
the hard-sphere a HS , as in all the SAFT-like equations of state. The model needs three
pure-component parameters for non-associating components and five for associating com-
seg
ponents. Those are the segment number mi , the segment diameter σi and the dispersion
energy ui /k B , and for an associating component with Ni association sites, the association
energy ε Ai Bi and the association volume κ Ai Bi of the association sites Ai and Bi are further
needed. PC-SAFT is extended to mixtures using the Berthelot–Lorentz combining rules, cf.
Equations (A4)–(A7), to estimate the interaction between two different components i and j.

1

σij = σ + σj (A4)
2 i


ui u j 1 − k ij ( T )
p
uij = (A5)

ε Ai Bi + ε A j Bj
ε Ai B j = (A6)
2
√ !2
p σi σj
κ Ai B j A B
= κ i iκ A j B j
1

(A7)
2 σi + σj

The binary interaction parameter k ij is described as a linear function of the temperature

according to Equation (A8).

k ij ( T ) = k ij,298.15K + k ij,T ( T/K − 298.15 K ) (A8)

The fugacity coefficient of component i (at T, p, x) is calculated from ares , (all) the
derivatives (∂ares /∂xi ) T,v,xk6=i and the compressibility factor Z using Equation (A9).
!
N
∂ares ∂ares
 
ln ϕi = a res
+ ( Z − 1) + − ∑ xj − ln Z (A9)
∂xi T,ρ,xk6=i j =1
∂x j
T,ρ,xk6= j
Molecules 2023, 28, 1768 16 of 20

Since ares and (∂ares /∂xi ) T,v,xk6=i are the explicit function of T, ρ, x (and not T, p, x),
one needs, in advance, to calculate the number density ρ corresponding to the pressure p,
ρ = ρ( T, p, x ), by iteratively solving Equation (A10).
"  res  #
∂a
p = k B Tρ 1 + ρ (A10)
∂ρ T,ρ,xk6=i

The whole program was written in FORTRAN. All the derivative properties in
Equations (A9) and (A10) were calculated by means of automatic differentiation using
dual numbers [96].

References
1. Toikka, A.M.; Samarov, A.A.; Toikka, M.A. Phase and chemical equilibria in multicomponent fluid systems with a chemical
reaction. Russ. Chem. Rev. 2015, 84, 378–392. [CrossRef]
2. Gmehling, J.; Kolbe, B. Thermodynamik, 2nd überarbeitete Auflage ed; VCH: Weinheim, Germany, 1992; ISBN 3527285474.
3. Smith, J.M.; van Ness, H.C.; Abbott, M.M. Introduction to Chemical Engineering Thermodynamics, 7th ed.; McGraw-Hill:
Boston, MA, USA, 2005; ISBN 0073104450.
4. Prausnitz, J.M.; de Azevedo, E.G.; Lichtenthaler, R.N. Molecular Thermodynamics of Fluid-Phase Equilibria, 3rd ed.; Prentice Hall
PTR: Upper Saddle River, NJ, USA, 1999; ISBN 0139777458.
5. Sundmacher, K.; Kienle, A. Reactive Distillation: Status and Future Directions; Wiley-VCH: Weinheim, Germany, 2003;
ISBN 3527305793.
6. Górak, A.; Sorensen, E. Distillation: Fundamentals and Principles; Academic Press: Cambridge, MA, USA, 2014; ISBN 0123865484.
7. Górak, A.; Olujic, Z. Distillation: Equipment and Processes; Academic Press: Cambridge, MA, USA, 2014; ISBN 0123868793.
8. Serafimov, L.A.; Pisarenko, Y.A.; Kulov, N.N. Coupling chemical reaction with distillation: Thermodynamic analysis and practical
applications. Chem. Eng. Sci. 1999, 54, 1383–1388. [CrossRef]
9. Brouwer, T.; Blahusiak, M.; Babic, K.; Schuur, B. Reactive extraction and recovery of levulinic acid, formic acid and furfural from
aqueous solutions containing sulphuric acid. Sep. Purif. Technol. 2017, 185, 186–195. [CrossRef]
10. Maurer, G. Modeling the liquid–liquid equilibrium for the recovery of carboxylic acids from aqueous solutions. Fluid Phase
Equilibria 2006, 241, 86–95. [CrossRef]
11. Schulz, R.; Waluga, T. Reactive extraction. In Process Intensification by Reactive and Membrane-Assisted Separations, 2nd ed.; De
Gruyter: Berlin, Germany; Boston, MA, USA, 2022; ISBN 978-3-11-072045-7.
12. Berry, D.A.; Ng, K.M. Synthesis of reactive crystallization processes. AIChE J. 1997, 43, 1737–1750. [CrossRef]
13. McDonald, M.A.; Salami, H.; Harris, P.R.; Lagerman, C.E.; Yang, X.; Bommarius, A.S.; Grover, M.A.; Rousseau, R.W. Reactive
crystallization: A review. React. Chem. Eng. 2021, 6, 364–400. [CrossRef]
14. Kenig, E.Y.; Schneider, R.; Górak, A. Reactive absorption: Optimal process design via optimal modelling. Chem. Eng. Sci. 2001,
56, 343–350. [CrossRef]
15. Kenig, E.Y.; Górak, A. Reactive absorption. In Integrated Chemical Processes: Synthesis, Operation, Analysis, and Control; Wiley:
Hoboken, NJ, USA, 2005; pp. 265–311.
16. Kunze, A.-K. Reactive absorption. In Process Intensification by Reactive and Membrane-assisted Separations, 2nd ed.; De Gruyter:
Berlin, Germany; Boston, MA, USA, 2022; ISBN 978-3-11-072045-7.
17. Skiborowski, M.; Górak, A. Hybrid separation processes. In Process Intensification by Reactive and Membrane-assisted Separations,
2nd ed.; De Gruyter: Berlin, Germany; Boston, MA, USA, 2022; ISBN 978-3-11-072045-7.
18. Schembecker, G.; Tlatlik, S. Process synthesis for reactive separations. Chem. Eng. Process. 2003, 42, 179–189. [CrossRef]
19. Malone, M.F.; Huss, R.S.; Doherty, M.F. Green chemical engineering aspects of reactive distillation. Environ. Sci. Technol. 2003,
37, 5325–5329. [CrossRef]
20. Nakashima, K.K. Chemistry of Active Coacervate Droplets: Liquid Droplets as a Minimal Model of Life. Ph.D. Thesis, Radboud
University Nijmegen, Nijmegen, The Netherlands, 2021.
21. Nakashima, K.K.; Baaij, J.F.; Spruijt, E. Reversible generation of coacervate droplets in an enzymatic network. Soft Matter 2018,
14, 361–367. [CrossRef]
22. Kim, Y.; Park, K.; Lee, H.; Jang, S.; Song, H.-C.; Shin, H.-C.; Park, J.J.; Park, J.; Maken, S. Purification of native and modified
enzymes using a reactive aqueous two-phase system. J. Ind. Eng. Chem. 2004, 10, 384–388.
23. Campos-García, V.R.; Benavides, J.; González-Valdez, J. Reactive aqueous two-phase systems for the production and purification
of PEGylated proteins. Electron. J. Biotechnol. 2021, 54, 60–68. [CrossRef]
24. Schick, D.; Bierhaus, L.; Strangmann, A.; Figiel, P.; Sadowski, G.; Held, C. Predicting CO2 solubility in aqueous and organic
electrolyte solutions with ePC-SAFT advanced. Fluid Phase Equilibria 2023, 567, 113714. [CrossRef]
25. NguyenHuynh, D.; Mai, C.T.Q.; Tran, S.T.K.; Nguyen, X.T.T.; Baudouin, O. Modelling of phase behavior of ammonia and its
mixtures using the mg-SAFT. Fluid Phase Equilibria 2020, 523, 112689. [CrossRef]
Molecules 2023, 28, 1768 17 of 20

26. Kontogeorgis, G.M.; Folas, G.K. Thermodynamic Models for Industrial Applications: From Classical and Advanced Mixing Rules to
Association Theories; John Wiley & Sons: Hoboken, NJ, USA, 2009; ISBN 0470747544.
27. Danzer, A.; Enders, S. Comparison of two modelling approaches for the interfacial tension of binary aqueous mixtures. J. Mol. Liq.
2018, 266, 309–320. [CrossRef]
28. Borrmann, D.; Danzer, A.; Sadowski, G. Generalized Diffusion–Relaxation Model for Solvent Sorption in Polymers. Ind. Eng.
Chem. Res. 2021, 60, 15766–15781. [CrossRef]
29. Caram, H.S.; Scriven, L.E. Non-unique reaction equilibria in non-ideal systems. Chem. Eng. Sci. 1976, 31, 163–168. [CrossRef]
30. Othmer, H.G. Nonuniqueness of equilibria in closed reacting systems. Chem. Eng. Sci. 1976, 31, 993–1003. [CrossRef]
31. Heidemann, R.A. Non-uniqueness in phase and reaction equilibrium computations. Chem. Eng. Sci. 1978, 33, 1517–1528.
[CrossRef]
32. Ung, S.; Doherty, M.F. Theory of phase equilibria in multireaction systems. Chem. Eng. Sci. 1995, 50, 3201–3216. [CrossRef]
33. Barbosa, D.; Doherty, M.F. A new set of composition variables for the representation of reactive-phase diagrams. Proc. R. Soc.
London. Ser. A Math. Phys. Sci. 1987, 413, 459–464.
34. Jiang, Y.; Smith, W.R.; Chapman, G.R. Global optimality conditions and their geometric interpretation for the chemical and phase
equilibrium problem. SIAM J. Optim. 1995, 5, 813–834. [CrossRef]
35. Jiang, Y.; Chapman, G.R.; Smith, W.R. On the geometry of chemical reaction and phase equilibria. Fluid Phase Equilibria 1996,
118, 77–102. [CrossRef]
36. Smith, W.R.; Missen, R.W. Strategies for solving the chemical equilibrium problem and an efficient microcomputer-based
algorithm. Can. J. Chem. Eng. 1988, 66, 591–598. [CrossRef]
37. Smith, J.V.; Missen, R.W.; Smith, W.R. General optimality criteria for multiphase multireaction chemical equilibrium. AIChE J.
1993, 39, 707–710. [CrossRef]
38. Smith, W.R. The computation of chemical equilibria in complex systems. Ind. Eng. Chem. Fundam. 1980, 19, 1–10. [CrossRef]
39. Zeleznik, F.J.; Gordon, S. Calculation of complex chemical equilibria. Ind. Eng. Chem. 1968, 60, 27–57. [CrossRef]
40. Gautam, R.; Wareck, J.S. Computation of physical and chemical equilibria—Alternate specifications. Comput. Chem. Eng. 1986,
10, 143–151. [CrossRef]
41. Barbosa, D.; Doherty, M.F. Theory of phase diagrams and azeotropic conditions for two-phase reactive systems. Proc. R. Soc.
London. Ser. A. Math. Phys. Sci. 1987, 413, 443–458.
42. Barbosa, D.; Doherty, M.F. The influence of equilibrium chemical reactions on vapor—Liquid phase diagrams. Chem. Eng. Sci.
1988, 43, 529–540. [CrossRef]
43. Zharov, V.T. Open evaporation of solutions of reacting substances. Zh. Fiz. Khim 1970, 44, 1967.
44. Zharov, V.T.; Pervukhin, O.K. Structure of the Vapor–liquid Equilibrium Diagrams of Reactive Systems: II. Methanol–Formic
Acid–Methyl Formate–Water System. Zh. Fiz. Khim 1972, 46, 1970.
45. Wasylkiewicz, S.K.; Ung, S. Global phase stability analysis for heterogeneous reactive mixtures and calculation of reactive
liquid–liquid and vapor–liquid–liquid equilibria. Fluid Phase Equilibria 2000, 175, 253–272. [CrossRef]
46. Okasinski, M.J.; Doherty, M.F. Thermodynamic behavior of reactive azeotropes. AIChE J. 1997, 43, 2227–2238. [CrossRef]
47. Ung, S.; Doherty, M.F. Necessary and sufficient conditions for reactive azeotropes in multireaction mixtures. AIChE J. 1995,
41, 2383–2392. [CrossRef]
48. Ung, S.; Doherty, M.F. Vapor-liquid phase equilibrium in systems with multiple chemical reactions. Chem. Eng. Sci. 1995,
50, 23–48. [CrossRef]
49. McDonald, C.M.; Floudas, C.A. Global optimization for the phase and chemical equilibrium problem: Application to the NRTL
equation. Comput. Chem. Eng. 1995, 19, 1111–1139. [CrossRef]
50. McDonald, C.M.; Floudas, C.A. Global optimization for the phase stability problem. AIChE J. 1995, 41, 1798–1814. [CrossRef]
51. McDonald, C.M.; Floudas, C.A. GLOPEQ: A new computational tool for the phase and chemical equilibrium problem. Comput.
Chem. Eng. 1997, 21, 1–23. [CrossRef]
52. Jalali-Farahani, F.; Seader, J.D. Use of homotopy-continuation method in stability analysis of multiphase, reacting systems.
Comput. Chem. Eng. 2000, 24, 1997–2008. [CrossRef]
53. Tsanas, C.; Stenby, E.H.; Yan, W. Calculation of multiphase chemical equilibrium by the modified RAND method. Ind. Eng. Chem.
Res. 2017, 56, 11983–11995. [CrossRef]
54. Stateva, R.P.; Wakeham, W.A. Phase equilibrium calculations for chemically reacting systems. Ind. Eng. Chem. Res. 1997,
36, 5474–5482. [CrossRef]
55. Sanderson, R.V.; Chien, H.H. Simultaneous chemical and phase equilibrium calculation. Ind. Eng. Chem. Process Des. Dev. 1973,
12, 81–85. [CrossRef]
56. Coatléven, J.; Michel, A. A successive substitution approach with embedded phase stability for simultaneous chemical and phase
equilibrium calculations. Comput. Chem. Eng. 2022, 168, 108041. [CrossRef]
57. Gupta, A.K.; Bishnoi, P.R.; Kalogerakis, N. A method for the simultaneous phase equilibria and stability calculations for
multiphase reacting and non-reacting systems. Fluid Ph. Equilibria 1991, 63, 65–89. [CrossRef]
58. White, W.B.; Johnson, S.M.; Dantzig, G.B. Chemical Equilibrium in Complex Mixtures. J. Chem. Phys. 1958, 28, 751–755. [CrossRef]
Molecules 2023, 28, 1768 18 of 20

59. Liu, Q.; Proust, C.; Gomez, F.; Luart, D.; Len, C. The prediction multi-phase, multi reactant equilibria by minimizing the Gibbs
energy of the system: Review of available techniques and proposal of a new method based on a Monte Carlo technique. Chem.
Eng. Sci. 2020, 216, 115433. [CrossRef]
60. Koulocheris, V.; Panteli, M.; Petropoulou, E.; Louli, V.; Voutsas, E. Modeling of Simultaneous Chemical and Phase Equilibria in
Systems Involving Non-reactive and Reactive Azeotropes. Ind. Eng. Chem. Res. 2020, 59, 8836–8847. [CrossRef]
61. Leal, A.M.M.; Kulik, D.A.; Smith, W.R.; Saar, M.O. An overview of computational methods for chemical equilibrium and kinetic
calculations for geochemical and reactive transport modeling. Pure Appl. Chem. 2017, 89, 597–643. [CrossRef]
62. Tsanas, C.; Stenby, E.H.; Yan, W. Calculation of simultaneous chemical and phase equilibrium by the method of Lagrange
multipliers. Chem. Eng. Sci. 2017, 174, 112–126. [CrossRef]
63. Zhang, H. A Review on Global Optimization Methods for Phase Equilibrium Modeling and Calculations. Open Thermodyn. J.
2011, 5, 71–92. [CrossRef]
64. Toikka, A.M.; Toikka, M.A. Solubility and critical phenomena in reactive liquid–liquid systems. Pure Appl. Chem. 2009,
81, 1591–1602. [CrossRef]
65. Toikka, M.A.; Toikka, A.M. Peculiarities of phase diagrams of reactive liquid–liquid systems. Pure Appl. Chem. 2012, 85, 277–288.
[CrossRef]
66. Toikka, A.M.; Toikka, M.A.; Trofimova, M.A. Chemical equilibrium in a heterogeneous fluid phase system: Thermodynamic
regularities and topology of phase diagrams. Russ. Chem. Bull. 2012, 61, 741–751. [CrossRef]
67. Toikka, A.M.; Toikka, M.A.; Pisarenko, Y.A.; Serafimov, L.A. Vapor-liquid equilibria in systems with esterification reaction. Theor.
Found. Chem. Eng. 2009, 43, 129–142. [CrossRef]
68. Gromov, D.; Toikka, A. Toward formal analysis of thermodynamic stability: Le Chatelier—Brown principle. Entropy 2020,
22, 1113. [CrossRef]
69. Toikka, A.M.; Jenkins, J.D. Conditions of thermodynamic equilibrium and stability as a basis for the practical calculation of
vapour–liquid equilibria. Chem. Eng. J. 2002, 89, 1–27. [CrossRef]
70. Gorovits, B.I.; Toikka, A.M.; Pisarenko, Y.A.; Serafimov, L.A. Thermodynamics of heterogeneous systems with chemical interaction.
Theor. Found. Chem. Eng. 2006, 40, 239–244. [CrossRef]
71. Toikka, M.A.; Kuzmenko, P.; Samarov, A.; Trofimova, M. Phase behavior of the oleic acid–methanol–methyl oleate–water mixture
as a promising model system for biodiesel production: Brief data review and new results at 303.15 K and atmospheric pressure.
Fuel 2022, 319, 123730. [CrossRef]
72. Senina, A.; Samarov, A.; Toikka, M.; Toikka, A. Chemical equilibria in the quaternary reactive mixtures and liquid phase splitting:
A system with n-amyl acetate synthesis reaction at 318.15 K and 101.3 kPa. J. Mol. Liq. 2022, 345, 118246. [CrossRef]
73. Toikka, M.A.; Tsvetov, N.S.; Toikka, A.M. Experimental study of chemical equilibrium and vapor-liquid equilibrium calculation
for chemical-equilibrium states of the n-propanol-acetic acid-n-propyl acetate-water system. Theor. Found. Chem. Eng. 2013,
47, 554–562. [CrossRef]
74. Samarov, A.; Prikhodko, I.; Shner, N.; Sadowski, G.; Held, C.; Toikka, A. Liquid–Liquid Equilibria for Separation of Alcohols from
Esters Using Deep Eutectic Solvents Based on Choline Chloride: Experimental Study and Thermodynamic Modeling. J. Chem.
Eng. Data 2019, 64, 6049–6059. [CrossRef]
75. Samarov, A.; Naumkin, P.; Toikka, A. Chemical equilibrium for the reactive system acetic acid+ n-butanol+ n-butyl acetate+ water
at 308.15 K. Fluid Ph. Equilibria 2015, 403, 10–13. [CrossRef]
76. Golikova, A.; Samarov, A.; Trofimova, M.; Rabdano, S.; Toikka, M.; Pervukhin, O.; Toikka, A. Chemical equilibrium for the
reacting system acetic acid–ethanol–ethyl acetate–water at 303.15 K, 313.15 K and 323.15 K. J. Solut. Chem. 2017, 46, 374–387.
[CrossRef]
77. Grob, S.; Hasse, H. Thermodynamics of phase and chemical equilibrium in a strongly nonideal esterification system. J. Chem. Eng.
Data 2005, 50, 92–101. [CrossRef]
78. Riechert, O.; Husham, M.; Sadowski, G.; Zeiner, T. Solvent effects on esterification equilibria. AIChE J. 2015, 61, 3000–3011.
[CrossRef]
79. Wangler, A.; Canales, R.; Held, C.; Luong, T.Q.; Winter, R.; Zaitsau, D.H.; Verevkin, S.P.; Sadowski, G. Co-solvent effects on
reaction rate and reaction equilibrium of an enzymatic peptide hydrolysis. Phys. Chem. Chem. Phys. 2018, 20, 11317–11326.
[CrossRef]
80. Gajardo-Parra, N.; Akrofi-Mantey, H.O.; Ascani, M.; Cea-Klapp, E.; Garrido, J.M.; Sadowski, G.; Held, C. Osmolyte effect
on enzymatic stability and reaction equilibrium of formate dehydrogenase. Phys. Chem. Chem. Phys. 2022, 24, 27930–27939.
[CrossRef]
81. Wangler, A.; Böttcher, D.; Hüser, A.; Sadowski, G.; Held, C. Prediction and Experimental Validation of Co-Solvent Influence on
Michaelis Constants: A Thermodynamic Activity-Based Approach. Chem. A Eur. J. 2018, 24, 16418–16425. [CrossRef]
82. Wangler, A.; Bunse, M.J.; Sadowski, G.; Held, C. Thermodynamic activity-based Michaelis constants. In Kinetics of Enzymatic
Synthesis; IntechOpen: London, UK, 2018; pp. 27–49.
83. Jaworek, M.W.; Gajardo-Parra, N.F.; Sadowski, G.; Winter, R.; Held, C. Boosting the kinetic efficiency of formate dehydrogenase
by combining the effects of temperature, high pressure and co-solvent mixtures. Colloids Surf. B Biointerfaces 2021, 208, 112127.
[CrossRef]
84. Michelsen, M.L. The isothermal flash problem. Part I. Stability. Fluid Phase Equilibria 1982, 9, 1–19. [CrossRef]
Molecules 2023, 28, 1768 19 of 20

85. Michelsen, M.L. The isothermal flash problem. Part II. Phase-split calculation. Fluid Phase Equilibria 1982, 9, 21–40. [CrossRef]
86. Alsaifi, N.M.; Englezos, P. Prediction of multiphase equilibrium using the PC-SAFT equation of state and simultaneous testing of
phase stability. Fluid Ph. Equilibria 2011, 302, 169–178. [CrossRef]
87. Boston, J.F.; Britt, H.I. A radically different formulation and solution of the single-stage flash problem. Comput. Chem. Eng. 1978,
2, 109–122. [CrossRef]
88. Xiao, W.; Zhu, K.; Yuan, W.; Chien, H.H. An algorithm for simultaneous chemical and phase equilibrium calculation. AIChE J.
1989, 35, 1813–1820. [CrossRef]
89. Sandler, S.I. Chemical and Engineering Thermodynamics, 3rd ed.; Section 8.5; J. Wiley & Sons Inc.: Hoboken, NJ, USA, 1999.
90. Smith, W.R.; Missen, R.W. Chemical Reaction Equilibrium Analisis: Theory and Algorithms; Wiley-Interscience: New York, NY, USA, 1982.
91. Ascani, M.; Held, C. Thermodynamics for reactive separations. In Process Intensification by Reactive and Membrane-Assisted
Separations, 2nd ed.; De Gruyter: Berlin, Germany; Boston, MA, USA, 2022; ISBN 978-3-11-072045-7.
92. Storonkin, A.V. Thermodynamics of Heterogeneous Systems; Part 1&2; Publishing House of Leningrad University: Leningrad, Russia, 1967.
93. Ascani, M.; Pabsch, D.; Klinksiek, M.; Gajardo-Parra, N.; Sadowski, G.; Held, C. Prediction of pH in multiphase multicomponent
systems with ePC-SAFT advanced. Chem. Commun. 2022, 58, 8436–8439. [CrossRef]
94. Ascani, M.; Sadowski, G.; Held, C. Calculation of Multiphase Equilibria Containing Mixed Solvents and Mixed Electrolytes:
General Formulation and Case Studies. J. Chem. Eng. Data 2022, 67, 1972–1984. [CrossRef]
95. Broyden, C.G. A class of methods for solving nonlinear simultaneous equations. Math. Comput. 1965, 19, 577–593. [CrossRef]
96. Yu, W.; Blair, M. DNAD, a simple tool for automatic differentiation of Fortran codes using dual numbers. Comput. Phys. Commun.
2013, 184, 1446–1452. [CrossRef]
97. Schmitt, M. Heterogen Katalysierte Reaktivdestillation: Stoffdaten, Experimente, Simulation und Scale-up am Beispiel der
Synthese von Hexylacetat. Ph.D. Thesis, Universität Stuttgart, Stuttgard, Germany, 2006.
98. Schmitt, M.; Hasse, H. Phase equlibria for hexyl acetate reactive distillation. J. Chem. Eng. Data 2005, 50, 1677–1683. [CrossRef]
99. Schmitt, M.; Hasse, H. Chemical equilibrium and reaction kinetics of heterogeneously catalyzed n-hexyl acetate esterification. Ind.
Eng. Chem. Res. 2006, 45, 4123–4132. [CrossRef]
100. Stephenson, R.; Stuart, J. Mutual binary solubilities: Water-alcohols and water-esters. J. Chem. Eng. Data 1986, 31, 56–70.
[CrossRef]
101. Stephenson, R.; Stuart, J.; Tabak, M. Mutual solubility of water and aliphatic alcohols. J. Chem. Eng. Data 1984, 29, 287–290.
[CrossRef]
102. Toikka, M.A.; Vernadskaya, V.; Samarov, A. Solubility, liquid-liquid equilibrium and critical states for quaternary system acetic
acid–n-amyl alcohol–n-amyl acetate–water at 303.15 K and atmospheric pressure. Fluid Phase Equilibria 2018, 471, 68–73. [CrossRef]
103. Esquivel, M.M.; Bernardo-Gil, M.G. Liquid—Liquid equilibria for the systems: Water/1-pentanol/acetic acid and water/1-
hexanol/acetic acid. Fluid Ph. Equilibria 1991, 62, 97–107. [CrossRef]
104. Cameretti, L.F.; Sadowski, G. Modeling of aqueous amino acid and polypeptide solutions with PC-SAFT. Chem. Eng. Process.
2008, 47, 1018–1025. [CrossRef]
105. Gross, J.; Sadowski, G. Application of the perturbed-chain SAFT equation of state to associating systems. Ind. Eng. Chem. Res.
2002, 41, 5510–5515. [CrossRef]
106. Tihic, A.; Kontogeorgis, G.M.; von Solms, N.; Michelsen, M.L. Applications of the simplified perturbed-chain SAFT equation of
state using an extended parameter table. Fluid Ph. Equilibria 2006, 248, 29–43. [CrossRef]
107. Pabsch, D.; Lindfeld, J.; Schwalm, J.; Strangmann, A.; Figiel, P.; Sadowski, G.; Held, C. Influence of solvent and salt on kinetics
and equilibrium of esterification reactions. Chem. Eng. Sci. 2022, 263, 118046. [CrossRef]
108. Veith, H.; Voges, M.; Held, C.; Albert, J. Measuring and Predicting the Extraction Behavior of Biogenic Formic Acid in Biphasic
Aqueous/Organic Reaction Mixtures. ACS Omega 2017, 2, 8982–8989. [CrossRef]
109. Gmehling, J.; Onken, U.; Arlt, W. Vapor-Liquid Equilibrium Data Collection: Organic Hydroxy Compounds: Alcohols and Phenols
(Chemistry Data Series, Volume 1, Part 2b); DECHEMA Research Institute: Frankfurt, Germany, 1978.
110. Lee, L.; Liang, S. Phase and reaction equilibria of acetic acid–1-pentanol–water–n-amyl acetate system at 760 mm Hg. Fluid Ph.
Equilibria 1998, 149, 57–74. [CrossRef]
111. Lee, M.-J.; Chen, S.-L.; Kang, C.-H.; Lin, H. Simultaneous chemical and phase equilibria for mixtures of acetic acid, amyl alcohol,
amyl acetate, and water. Ind. Eng. Chem. Res. 2000, 39, 4383–4391. [CrossRef]
112. Gross, J.; Sadowski, G. Perturbed-chain SAFT: An equation of state based on a perturbation theory for chain molecules. Ind. Eng.
Chem. Res. 2001, 40, 1244–1260. [CrossRef]
113. Zwanzig, R.W. High-temperature equation of state by a perturbation method. I. Nonpolar gases. J. Chem. Phys. 1954,
22, 1420–1426. [CrossRef]
114. McQuarrie, D.A. Statistical Mechanics; Sterling Publishing Company: New York, NY, USA, 2000; ISBN 1891389157.
115. Wertheim, M.S. Fluids with highly directional attractive forces. I. Statistical thermodynamics. J. Stat. Phys. 1984, 35, 19–34.
[CrossRef]
116. Wertheim, M.S. Fluids with highly directional attractive forces. II. Thermodynamic perturbation theory and integral equations. J.
Stat. Phys. 1984, 35, 35–47. [CrossRef]
Molecules 2023, 28, 1768 20 of 20

117. Wertheim, M.S. Fluids with highly directional attractive forces. III. Multiple attraction sites. J. Stat. Phys. 1986, 42, 459–476.
[CrossRef]
118. Wertheim, M.S. Fluids with highly directional attractive forces. IV. Equilibrium polymerization. J. Stat. Phys. 1986, 42, 477–492.
[CrossRef]

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